Radiation refers to the phenomenon of energy release and propagation (Du et al., 2023). Radiation can be categorized as either ionizing or non-ionizing. Ionizing radiation has greater energy, causing atoms or molecules in a substance to be ionized, leading to DNA damage, gene mutations, cell death, or carcinogenesis (Liu et al., 2023; Ortega et al., 2023). Radiation protection aims to take various measures to reduce or avoid the harm of radiation to human health and the environment. At present, radiation protection consists mainly of three approaches: physical protection, chemical protection, and biological protection (Yang et al., 2020). Among them, chemical protection is the use of specific compounds or elements to enhance organisms’ tolerance to radiation and reduce the harm caused by radiation (Andrady et al., 2023; Javadi et al., 2023).

Selenium (Se) plays a significant role in many physiological functions such as antioxidants, immune regulation, and thyroid hormone synthesis, as described in the report (Li et al., 2021a; Wu et al., 2021; Rao et al., 2022). Research has shown that Se downregulates inflammatory mediators TNF-α, IL-1β and IL-6 gene expressions via TLR2, NF-κB and MAPK signaling pathway in S. aureus-stimulated bMECs, which may be responsible for the anti-inflammatory effect of Se (Wang et al., 2018). As early as 1964, selenium compounds were discovered to have radiation protection effects. It protects organisms from radiation damage through mechanisms such as clearing free radicals, maintaining glutathione levels, and regulating signaling pathways (Shimazu et al., 1964). However, the bioavailability and activity of selenium are influenced by factors such as its chemical form, dosage, and distribution within the organism (Ragini and Arumugam, 2023). For example, In the form of organic selenium compounds, selenium exhibits radiation protection effects only at moderate concentrations, while higher concentrations are toxic to cells (Ragini and Arumugam, 2023). Moreover, selenium compounds demonstrate a combination of preventive (effective before exposure to ionizing radiation) and mitigating (effective after exposure to ionizing radiation, prior to the development of the first clinical signs of radiation sickness), demonstrating their multiple characteristics. Therefore, the development of efficient, safe, and stable selenium-based radiation protection agents is of critical significance.

Nanotechnology refers to the technology of utilizing nanoscale substances or structures to achieve novel functions or performance (El-Morsy et al., 2022). Nanotechnology has a wide range of potential uses in radiation protection due to its unique optical, electronic, magnetic, catalytic, and biological characteristics (Pan et al., 2022). For example, ZnO and TiO₂ nanoparticles demonstrate effectiveness in shielding against ultraviolet radiation by absorbing and blocking it, thus hindering its penetration into the tissues and cells of human (Cai et al., 2013; Khan et al., 2023). Moreover, another study has shown that CeO₂ nanoparticles protect gastrointestinal epithelial cells and human lymphocytes from ionizing radiation by reducing oxidative stress and inflammatory reactions (Tarnuzzer et al., 2005; Niu et al., 2007). These findings emphasize the potential of nanoparticles in safeguarding normal cells and tissues from radiation-induced harm. In recent years, nano selenium (Se NPs) has attracted much attention as a new type of selenium-based radiation protection agent. Se NPs exhibit remarkable antioxidant properties, capable of neutralizing free radicals induced by radiation, thereby reducing oxidative stress and protecting cells from damage (Pereira et al., 2022). Moreover, Se NPs has been reported to inhibit radiation-induced cell apoptosis, mitigating direct cellular damage caused by radiation exposure (Gudkov et al., 2023). Furthermore, Se NPs effectively mitigate radiation-induced inflammatory responses, thereby reducing cell death and tissue damage resulting from inflammation (Zahran et al., 2017). However, Se NPs also have some shortcomings, such as easy oxidation, instability, and difficulty controlling particle size (Carroll et al., 2020). Surface modification of Se NPs is therefore one of the most effective ways to enhance their radiation protection properties.

Polyvinylpyrrolidone (PVP) is a commonly used biomedical polymer material with good water solubility, biocompatibility, low immunogenicity, and low toxicity (Ruiz-Fresneda et al., 2023). PVP can be used as an ideal surface modifier to improve the stability, dispersibility, and bioavailability of Se NPs. Previous studies have shown that treating rats with 5 or 10 Gy X-rays and then detecting their cardiopulmonary structure and physiological function can better describe the natural history of this injury (Ghosh et al., 2009). In this study, PVP-Se NPs are prepared by a chemical reduction method and tested in vitro and in vivo on human umbilical vein endothelial cells (HUVECs) and SD rats, respectively, for radiation protection. Meanwhile, Western blotting was conducted to measure the effects of PVP-Se NPs on HUVECs and MAPK-NF-κB pathway-related proteins in rats’ livers and kidneys, to provide novel preventive measures for radiation protection. These research results will contribute to a deeper understanding of PVP-Se NPs’ radiation protection potential.

Finding substances to prevent radiation damage remains one of the urgent focuses in radiation biology. Although the radiation resistance effects of a large number of compounds have been studied (Aygun et al., 2020; Kreusch and Duarte, 2021; Wang et al., 2023), Existing radiation protection methods still fail to fully meet the requirements, especially in terms of key characteristics such as efficiency, action time, flexibility, and usability (Kapustka, 2022). Due to selenium’s antioxidant properties, there is growing research focusing on its utilization in radiation protection. There are many similarities between selenium’s chemical properties and those of sulfur. Nevertheless, some selenium derivatives exhibit a significantly higher ability to scavenge free radicals and peroxides than similar sulfur compounds. Numerous studies have demonstrated Selenium’s antioxidant and protective properties. Selenium compounds protect biological molecules from oxidative stress (Li et al., 2023; Mamgain et al., 2023). However, conventional Se supplements present a range of challenges, including low absorption efficiency and elevated toxicity levels. Therefore, developing innovative systems as carriers of selenium compounds to improve selenium bioavailability and achieve controlled release in vivo is of significant significance.

Recent research has revealed that nano-modified inorganic compounds display antioxidant properties (Krishnan Nair et al., 2023). When utilized as therapeutic agents within the body, Se NPs can gradually release biologically available selenium in a controlled manner (Zhang et al., 2001). Compared to molecular forms of selenium, the toxicity of Se NPs is reduced by 50–100 times (Gao et al., 2023). In this study, we synthesized polyvinylpyrrolidone-modified selenium nanoparticles (PVP Se NPs) and explored their protective effects against radiation, along with their potential molecular mechanism. Previous research has suggested that even minimal concentrations of molecular selenium could pose damage to cells (Maynar et al., 2018). Hence, initial screening for the optimal PVP-Se NPs concentration becomes necessary. Experimental findings reveal that the optimal concentration of PVP-Se NPs for both in vitro and in vivo is 36 μg/mL.

It has reported that ionizing radiation can interact with cellular molecules, triggering an overproduction of free radicals and reactive oxygen species such as hydroxyl radicals, hydrogen peroxide, and superoxide radicals. This cascade of free radicals and reactive oxygen species induces oxidative stress (Shirazi et al., 2011). Oxidative stress damages biomacromolecules, disrupting cellular redox balance and impairing normal cellular function and homeostasis, ultimately culminating in cell death (Clavo et al., 2019). Additionally, ionizing radiation also has the ability to prompt the excessive release of inflammatory factors and activation of inflammatory signaling pathways (Baselet et al., 2019; Wijerathne et al., 2021). In this study, we found that PVP Se NPs significantly reduced the generation of MDA, IL-1, IL-6 and TNF-α increased the generation of GSH, SOD, CAT, and effectively alleviated cell apoptosis in HUVECs and rats. These findings collectively suggest that PVP Se NPs mitigate radiation-induced damage both in vitro and in vivo by alleviating oxidative stress, inflammatory responses, and cell apoptosis.

To further investigate the potential molecular mechanisms underlying the mitigation of radiation damage by PVP-Se NPs, we utilized Western blot analysis to assess the expression of proteins associated with the NF-κB and MAPK signaling pathways in HUVECs and rats. NF-κB serves as a pivotal nuclear transcription factor implicated in regulating various cellular processes, including proliferation, immunity, and inflammatory responses (Thakur and Ray, 2017). A prior study demonstrated that curcumin mitigates oxidative stress and inflammatory responses in rats by suppressing NF-κB signaling pathway activation, thus ameliorating radiation-induced liver damage (Li et al., 2021b). MAPK functions as a serine/threonine-specific protein kinase involved in regulating essential physiological and pathological cellular processes, including growth, differentiation, apoptosis, and inflammatory responses (Fecher et al., 2008). Ding et al., 2021 observed decreased Mast1 expression in gastric tissue irradiated mice. Through genetic manipulation experiments, they revealed that Mast1 upregulation inhibits p38 MAPK signaling pathway activation, thereby alleviating radiation-induced gastric damage in mice. Our experimental results reveal that PVP-Se NPs decreased the expression of p-IκB-α and p-p65 in the NF-κB signaling pathway, as well as p-JNK, p-ERK, and p-p38 in the MAPK signaling pathway. Consequently, we hypothesize that PVP-Se NPs might be involved in radiation protection by reducing oxidative stress and inflammatory factors by inhibiting NF-κB and MAPK pathways.

In summary, PVP-Se NPs can resist X-ray induced HUVECs cell damage and rat radiation damage, and have radiation protective effects both in vivo and in vitro. The mechanism may be related to reducing oxidative stress, inhibiting inflammatory factor expression, and regulating NF-κB and MAPK signaling pathway gene expression. We believe that future research should prioritize several key areas. Firstly, there is a need to optimize the synthesis methods of nanomaterials to enhance the stability and biocompatibility of PVP-Se NPs in vivo, while also minimizing potential toxicity and side effects. Secondly, clinical trials should be conducted to assess the radiation protection efficacy of PVP-Se NPs in humans. Thirdly, exploration of the potential application of PVP-Se NPs in protecting against radiation contamination could help safeguard both humans and ecosystems from radiation hazards. However, it's important to acknowledge the limitations of this study. Firstly, the investigation of the radiation protective effects of PVP-Se NPs in vitro was limited to only 1 cell line (HUVECs). Secondly, the evaluation of PVP-Se NPs’ radiation protection effects in vivo was restricted to the liver and kidney of rats. Thirdly, the analysis was focused solely on the expression of NF-κB and MAPK signaling pathway-related proteins in HUVECs and rats, with no rescued experiments conducted.